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By Ed Susman, Contributing Writer, MedPage Today Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse PlannerA short-term course of systemic glucocorticoid therapy in patients with acute chronic obstructive pulmonary disease (COPD) was as effective as treatment of longer duration.Point out that the findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD.PHILADELPHIA -- A short-term course of systemic glucocorticoid therapy in patients with acute chronic obstructive pulmonary disease (COPD) was as effective as treatment of longer duration, researchers reported here.
In a multicenter Swiss trial, a 5-day glucocorticoid treatment course achieved noninferiority (P=0.006 for noninferiority) when compared to a standard 14-day course among COPD patients presenting to the emergency department with exacerbations, reported Jorg Leuppi, MD, PhD, from University Hospital of Basel, and colleagues at the annual meeting of the American Thoracic Society.
Also, 35.9% of the patients on the short-course therapy reached the primary endpoint of time to exacerbation at 6-month follow-up versus 36.8% in the long-course group, they wrote in an article published simultaneously online in the Journal of the American Medical Association.
"There was no difference between groups in time to death, the combined end point of exacerbation, death, or both and recovery of lung function," the authors wrote. "These findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD."
International guidelines suggest 7- to 14-days of glucocorticoid therapy in these patients, but the optimal dose and duration are not known, the authors pointed out.
The REDUCE (Reduction in the Use of Corticosteroids in Exacerbated COPD) was conducted at five Swiss teaching hospitals. The study randomized 314 COPD patients who presented to the emergency department with acute exacerbations. Past and present smokers without a history of asthma were enrolled from 2006 to 2011. They were treated with 40 mg oral prednisone daily or matching placebo.
"The predefined noninferiority criterion was absolute increase in exacerbations of at most 15%, translating to a critical hazard ratio of 1.515 for a reference event rate of 50%," the authors explained.
Of the randomized patients, 289 were admitted to the hospital, 311 patients were included in the intention-to-treat analysis and 296 patients were included in the per-protocol analysis. The researchers observed that 56 patients experienced the primary endpoint of a COPD exacerbation in the short-term treatment group compared with 57 patients in the conventional treatment group.
In the intention-to-treat analysis, the hazard ratio for short-term versus long-term therapy was 0.95 (90% CI 0.70-1.29). In the per-protocol analysis, the HR was 0.93 (90% CI 0.68 60 1.26, P=0.005 for noninferiority).
Estimates of re-exacerbation rates within 180 days were 37.2% for the 5-day group and 38.4% for the 14-day group for a difference of -1.2%.
Among patients who did experience re-exacerbation, the median time to event was about 44 days in the short-term group and 29 days in the long-term group.
During hospital stay, there was no increase in the requirement for mechanical ventilation with the short-term regimen.
However, the authors did point out that in the long-term treatment arm, the "mean cumulative prednisone dose was significantly higher -- 793 mg versus 379 mg." While treatment-associated adverse reactions, such as hyperglycemia and hypertension, did not occur more frequently with the higher dose, the shorter course with less glucosteroid exposure is noteworthy.
"Long-term use of systemic glucocorticoids is an independent risk factor for increased mortality in COPD," they explained. "Given the adverse effects of glucocorticoids ... exposure should be minimized."
The study had some limitations. In addition to glucocorticoids, enrolled patients were treated with inhaled, long-acting beta-agonists and tiotropium throughout the trial so some of them may have been overtreated.
This "may explain the lower than expected re-exacerbation rates, implying that our power estimates may have been too high," the authors acknowledged.
Also, most of the patients had severe COPD so the results may not apply to those with less severe disease.
In an accompanying JAMA editorial, Don Sin, MD, and Hye Yun Park, MD, PhD, of the University of British Columbia in Vancouver, suggested that the trial's findings should override current international guidelines for treatment of acute COPD exacerbations.
"Until novel strategies are found, the study by Leuppi, et al, provides convincing evidence that less is more for steroid use in chronic obstructive pulmonary disease and that a 5-day regimen rather than the 10-day to 14-day course recommended by most national and international guidelines ... this is welcome news for patients for COPD who experience multiple exacerbations annually and are exposed to repeated course of systemic corticosteroids," they wrote.
The study was supported by government and academic grants and also received support from Viollier Laboratories and AstraZeneca.
Leuppi disclosed commercial relationships with AstraZeneca, Merck, Sharp and Dohme, Chibret, Nycomed, Novartis, Pharmaxis. Co-authors disclosed commercial relationships with Thermo Fisher Scientific, bioMerieux, Daiichi Sankyo, Eli Lilly, Merck, Sharp and Dohme, Chibret, GE, Phillips, sanofi-aventis, Bayer, Pfizer, Brahms, AstraZeneca, Viollier Laboratories.
Sin disclosed commercial relationships with Merck Frosst, Novartis Canada, AstraZeneca, Grifols, Boehringer Ingelheim and GlaxoSmithKline. Park reported no conflicts of interest.
In addition to glucocorticoids, enrolled patients were treated with inhaled, long-acting beta-agonists and tiotropium throughout the trial so some of them may have been overtreated.
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